One in nine women will develop breast cancer in her lifetime. This number will increase as the population ages and it is critical that preventive tools be identified to slow or halt this progression. Increasing physical activity or exercise has been suggested as a means of reducing a woman's risk for developing breast cancer. Although epidemiological data and animal mammary cancer models support the inverse relationship between exercise and breast cancer risk, the data are not entirely consistent. Further, the mechanism(s) that underlie exercise's effect are unknown. An Academic Career Development Award is sought to support training to expand the knowledge and experiential foundation of Dr. Kim Westerlind, an exercise physiologist, in mammary gland biology and carcinogenesis. This effort is sponsored by the primary mentor, Thomas J. Slaga, Ph.D. (AMC Cancer Research Center), and co-sponsors, Margaret Neville, Ph.D. (University of Colorado Health Sciences Center), and Gary Cutter, Ph.D. (AMC Cancer Research Center). The K07 award will provide the support and opportunity for the applicant to become an independent investigator in cancer prevention and control, with a particular emphasis linking exercise science and cancer prevention research. The proposed program includes structured education, research and teaching activities. The research projects proposed address the linkage between exercise and breast cancer, an area that holds significant promise for prevention and control. The research plan consists of a set of carefully-controlled animal experiments. The first series is designed to identify, control for, and/or eliminate confounders that impact exercise-cancer studies. These include: timing of exercise, housing practices, appropriate control groups, strain differences, and quantification of specific exercise components, specifically intensity, duration, and frequency. In addition, two models, treadmill exercise and voluntary wheel running, will be used and compared. The second series of experiments will focus on elucidating the mechanism(s) and biological markers of cancer inhibition in carefully designed exercise-training studies. The final series will focus on identifying specific components of exercise that are critical for inhibition of carcinogenesis. Ultimately, understanding mechanism(s) and identifying biological markers of cancer inhibition, will allow for the translation of the findings from the animals studies to controlled human-intervention and population-based studies.